Background: Substance abuse adds to diagnostic uncertainty in psychosis and may increase the risk of transition from brief and affective psychoses to schizophrenia.This study examined whether comorbid substance disorder was associated with diagnostic instability and progression from other psychosis diagnoses to schizophrenia and whether effects differed for cannabis and stimulant-related disorders. Method: We identified 24,306 individuals admitted to hospital with an lCD-JO psychosis diagnosis between 2000 and 2011. We examined agreement between initial diagnosis and final diagnosis over 2 5 years and predictors of diagnostic change toward and away from a final diagnosis of schizophrenia. Results: Nearly half (46%) of participants with initial briet atypical, or drug- induced psychoses were later diagnosed with schizophrenia. Persisting illicit drug disorders did not increase the likelihood of progression to schizophrenia (OR 0.97; 95% Cl, 0.89 1.04) but increased the likelihood of revision of index psychosis diagnosis away from schizophrenia (OR 1.55; 95% Cl, 1.40 1.71). Cannabis disorders predicted an increased likelihood of progression to schizophrenia (OR 1.12; 95% Cl, 1.01 1.24), while stimulant disorders predicted a reduced likelihood (OR 0.81; 95% Cl, 0.67 0.97). Stimulant disorders were associated with greater overall diagnostic instability. Conclusions: Many people with initial diagnoses of brief and affective psychoses are later diagnosed with schizophrenia. Cannabis disorders are associated with diagnostic instability and greater likelihood of progression to schizophrenia. By contrast, comorbid stimulant disorders may be associated with better prognosis in psychosis, and it may be important to avoid premature closure on a diagnosis of schizophrenia when stimulant disorders are present.